CB2 Agonists for Treatment of Neuropathic Pain.

用于治疗神经性疼痛的 CB2 激动剂。

基本信息

批准号：
7481321
负责人：
Anuradha Mahadevan
金额：
$ 13.05万
依托单位：
ORGANIX, INC.
依托单位国家：
美国
项目类别：
财政年份：
2008
资助国家：
美国
起止时间：
2008-08-01 至 2010-01-31
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/7481321
关键词：
Address Adverse effects Affinity Agonist Animal Model Binding Biological Assay CNR1 gene CNR2 gene Cannabinoids Catalepsy Chronic Clinical Treatment Clinical Trials Condition Development Disease Drug Delivery Systems Evaluation Expenditure GTP Binding Genetic Goals In Vitro Injury Knockout Mice Lead Lidocaine Patch Ligands Mediating Medical Modeling Mus Nervous system structure Neuraxis Neuropathy Norepinephrine Opioid Opioid Analgesics Outcome Pain Pain management Patients Peripheral Persistent pain Pharmaceutical Preparations Phase Population Quality of life Research Seizures Serotonin Standards of Weights and Measures System Tail Testing Tetrahydrocannabinol Thermal Hyperalgesias Tissues Tramadol Tricyclic Antidepressive Agents United States Food and Drug Administration Withdrawal Work Workplace analog base cannabinoid receptor chronic pain design gabapentin immune function in vivo inflammatory neuropathic pain inflammatory pain inhibitor/antagonist medical appointment mouse model natural hypothermia novel painful neuropathy prevent productivity loss receptor receptor binding response sciatic nerve uptake

项目摘要

DESCRIPTION (provided by applicant): Neuropathic pain is a type of chronic pain state caused by injury or disease to the nervous system. Annual medical spending due to pain has been estimated to be over $100 billion. Currently there are no medications available to prevent or cure this devastating disease condition. Hence, there is an urgent need to discover effective drugs to treat this chronic pain condition. A promising drug target for neuropathic pain is the cannabinoid CB2 receptor. In phase I of this proposal our focus will be on the optimization of our lead compound to discover one or more CB2 receptor agonists with high receptor affinity and selectivity. In order to distinguish between agonist and antagonist activity, analogs that bind effectively to the CB2 receptor, will be evaluated for their ability to stimulate [35S]GTP?S binding. Our specific goal is to develop one or more lead CB2 agonists that show good activity and efficacy in an animal model for neuropathic pain. If this goal is accomplished in Phase I, we will have a drug candidate for further development in Phase II. The long-term goal of this proposal is to develop a medication for neuropathic pain that is effective and without undesirable side effects.

描述（由申请人提供）：神经性疼痛是一种由神经系统损伤或疾病引起的慢性疼痛状态。据估计，每年因疼痛导致的医疗支出超过 1000 亿美元。目前没有药物可以预防或治愈这种毁灭性的疾病。因此，迫切需要发现治疗这种慢性疼痛的有效药物。治疗神经性疼痛的一个有前景的药物靶点是大麻素 CB2 受体。在该提案的第一阶段，我们的重点将是优化我们的先导化合物，以发现一种或多种具有高受体亲和力和选择性的 CB2 受体激动剂。为了区分激动剂和拮抗剂活性，将评估与CB2受体有效结合的类似物刺激[35S]GTPαS结合的能力。我们的具体目标是开发一种或多种先导 CB2 激动剂，这些激动剂在神经性疼痛动物模型中表现出良好的活性和功效。如果第一阶段实现了这一目标，我们将在第二阶段有进一步开发的候选药物。该提案的长期目标是开发一种有效且无不良副作用的神经性疼痛药物。